Stille coupling intramolecular

An intramolecular variant of the Stille coupling is suitable for the construction of macrocycles. An example is the ring-closing step to form a 14-membered lactone ring 8 in a synthesis of zearalenone as reported by Stille et al. ... 

A distinguishing feature of the Nicolaou synthesis of rapamycin is the use of a palladium-mediated tandem inter-/intramolecular Stille coupling to construct rapamycin s 31-membered macrolide ring and conjugated triene moiety. This maneuver was unprecedented in the macrolide field,9 and it can be applied to a fully deprotected seco substrate (vide infra). 

Scheme 37. Baldwin s approach to y-oxo-a,/ -unsaturated macrocycles by intramolecular Stille coupling.

Our strategy is based on the premise that the 31-membered ring and the conjugated triene array of the natural product could be fashioned simultaneously by a tandem inter-/intramolecular Stille coupling. Moreover, the mild conditions under which Stille couplings can be performed fueled hopes that the crucial stitching cycliza-tion could be conducted on a fully deprotected seco bis(vinyl iodide) (see 145, Schemes 40 and 54) the stitching cyclization would thus be the final operation in the synthesis. 

Wong reported that stoichiometric amounts of copper(I) chloride alone can promote the intramolecular Stille coupling (equation 138)243. In fact, copper(I)-mediated reaction was cleaner and faster compared with that catalysed by Pd(0) species. Selected examples of intermolecular Stille coupling reactions leading to dienes (Table 25)236a,242b 244, polyenes (Table 26)245 and macrocyclizations (Table 27)246 are given in the respective tables. 

TABLE 27. Intramolecular cyclizations through Stille coupling... 

The stereoselective synthesis of the 12-acetoxy enone 428, related to the limonoid azadiradione, has been achieved in 12 steps (16% overall yield), starting from tricyclic diester 429. The key steps involve an intramolecular 1,3-dipolar cycloaddition of a nitrile oxide and a Stille coupling reaction of vinyl iodide with stannylfuran (469). 

In Grigg s approach to hippadine (37), he established the connection between the two phenyl rings via the Stille-Kelly reaction [45]. When diiodide 35 was submitted to the Pd(0)/ditin catalyst system, the intramolecular cyclization was realized to establish the C—C bond in lactam 36. Oxidation of the indoline moiety in 36 using 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) then delivered hippadine (37). Analogously, the intramolecular Stille coupling of dibromide 38 led directly to hippadine (37) [46]. 

These workers also synthesized tryptamine stannane 161 and effected Stille couplings with this compound, including the intramolecular reaction 162 to 163 [171]. Eight- and 9-membered rings could also be fashioned in this manner. Other Pd catalysts were much less successful. The N-tosyl derivative of 162 was similarly prepared and used in Stille chemistry. 

Starting with the intermediate ( )-145 of the aforementioned total synthesis of ( )-122, Piers realized the synthetic access to the racemic dolastane ( )-124 (Scheme 22) [82, 83]. An intramolecular Stille coupling served as key step, this time for the annulation of the C-ring. 

The formation of seven membered heterocycles and larger rings through cross-coupling reactions is quite rare (except for some macrocyclic natural products). An example of such a process is presented in 5.1. The intramolecular Stille-coupling of the tributylstannyl-indole and vinyl bromide moieties led to the formation of a seven membered ring in good yield.1... 

The furyl- and benzofurylstannanes can be coupled with a variety of electrophiles including aryl [53] and heteroaryl halides [54, 55]. In their synthetic studies towards lophotoxin and pukalide, Paterson and coworkers explored both intermolecular and intramolecular Stille coupling reactions [56]. The intermolecular approach between vinyl iodide 54 and furylstannane 55 was... 

The palladium-catalyzed coupling of aryl iodides with vinylstannanes (Stille coupling) leads to the formation of styrenes. With resin-bound vinylstannanes, this reaction can be conducted in such a way that simultaneous detachment from the support of the newly formed styrenes occurs. This has been realized intramolecularly in the preparation of macrocyclic lactones (Entry 4, Table 3.43). The required resin-bound vinylstannanes were prepared either by hydrostannylation of alkynes with a resin-... 

An intramolecular Stille coupling of tributyl(3-(2-iodobenzyloxy)prop-l-en-2-yl)stannane 154 at 90 °C affords 4-methyl-177-isochromene in good yield (Equation 71) <2004JOC468>. 

The intramolecular Stille coupling of tributyl(3-(2-iodobenzyloxy)prop-l-en-2-yl)stannane 572 provides 4-methyl-eneisochroman 573 in good yield, with careful control of the reaction temperature necessary to prevent isomerization of the double bond to form 4-methylisochromene (Scheme 124) <2004JOC468>. 4-Methyleneisochroman 573 can also be synthesized via an indium-mediated intramolecular cyclization of 2-bromoallyloxymethyl iodobenzene 574 in excellent yield (Scheme 124) <20050L343>. 

The fused indoles 91 (n = 1-3) have been synthesized by Stille coupling of the stannylbenzene 92 with 2-iodo-2-enones 93, followed by intramolecular palladium-catalyzed... 

Scheme 67 Sequential stannylation-intramolecular Stille coupling [127] (bonds formed by Stille coupling are drawn in bold lines)...

During the synthesis of such compounds, the epoxide is often installed at an early stage for example, dihydroquinoline 31 (Scheme 18) is readily epoxidized with MCPBA, and subsequent formation of the bis-alkynyl iodides followed by bis-intramolecular Stille coupling occurs with complete chemoselectivity <2006ARK261>. 

Another intriguing cascade, of an intramolecular Heck type followed by an intermolecular Stille coupling, produces the dienyne 80 starting from the enyne 78 and the stannane 79 (Scheme 3-24) [175]. The reversed sequence of a Stille-type followed by a... 

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